Ca2+-dependent activation of tyrosine hydroxylase involves MEK1

Tyrosine hydroxylase (TOH) activity is regulated acutely by phosphorylation of serines 8, 19, 31 and 40. The only kinases known to phosphorylate Ser31 are the mitogen-activated protein kinases MAPK-1 and 2. The involvement of these kinases in TOH activation in situ was therefore investigated using i ntact bovine chromaffin cells. Nicotine, K+ and A23187 increased TOH activi ty over 10 min in a Ca2+-dependent manner. The response to all three was re duced by PID098059, a selective inhibitor of the upstream activator of MAPK , MEK1. In contrast, TOH activation by forskolin and phorbol dibutyrate wer e unaffected by PD098059. The results support a key role for MEK1/MAPK in t he acute activation of TOH by nicotinic receptors and by other agonists tha t increase cytosolic Ca2+. NeuroReport 12:2679-2683 (C) 2001 Lippincott Wil liams & Wilkins.